Natural Hormone Replacement Therapy
Natural hormone replacement therapy (NHRT) is the use of non-synthetic, bio-identical hormones (estrogens, progesterone, and/or testosterone), derived from plants), to treat hormone imbalances and deficiencies. The first oral contraceptive pill was originally derived from Dioscorea species, wild yam; later soy was used as the precursor for oral contraceptive hormones.
Chinese medicine has made use of phytohormones for thousands of years. Natural progesterone was first crystallized from plants in 1938. NHRT was developed in the late 1970s and became available commercially in the early 1980s. By 1989 micronized (very finely ground) progesterone was developed for better absorption into the bloodstream. The use of NHRT has increased as women have become increasingly dissatisfied with conventional hormone replacement therapy (HRT) because of ineffectiveness, side effects, and/or growing concerns about risks, especially breast and uterine cancer risk.
NHRT often alleviates symptoms of hormone imbalances and deficiencies that may occur at any stage of
- heart disease
- bone loss and osteoporosis
- digestive problems
- high cholesterol levels
- Alzheimer's disease
Some researchers claim that NHRT may slow the aging process and help prevent:
- fibroblastic or lumpy breasts
- heart disease
Reported benefits of testosterone NHRT therapy in men include:
- increased muscle mass and lower body fat
- increased sex drive
- increased energy levels
- improved concentration and productivity
Human sex hormones
The major steroid sex hormones—estrogen, progesterone, and testosterone—control gender and the aging process. They help maintain health and have profound effects on emotions and behavior. Cells throughout the body have receptor molecules on their surfaces that bind specific hormones. Receptor-binding causes a series of reactions within the cell that are specific for the hormone and cell type.
In the human body cholesterol is converted into pregnenolone, which is converted into both progesterone and dehydroepiandrosterone (DHEA). These hormones, in turn, can be converted into estrogens, testosterone, and other hormones.
High levels of sex hormones are produced in the developing fetus and then almost disappear until puberty. Estrogen and progesterone are at high levels during the reproductive years and are extremely high during pregnancy. With aging, the levels of sex hormones decline. When ovulation ceases at menopause, progesterone production drops to very low levels. Estrogen and progesterone have opposing effects in the body, balancing each other. At various times in their lives, many women experience hormone imbalances or sudden changes in hormone levels. During menopause the ratio of estrogen to progesterone may increase. During andropause the ratio of testosterone to estrogen may decline.
Although the body produces many forms of estrogen, the term usually refers to the three major types:
- Estriol is the weakest estrogen.
- Estradiol is the most active estrogen. Nearly every cell in the body has estradiol receptors, making it extremely important for cell and organ function.
- Estrone is made from testosterone derivatives in fat cells of postmenopausal women.
The body also produces several different types of testosterone.
The hormones used in NHRT are considered to be "bioidentical" to human sex hormones. The chemical formulae of NHRT hormones are identical to the corresponding hormones produced in the human body. They are very similar or identical to human hormones in their chemical structures, modes of action, and interactions with cell-surface receptors and other hormones. Receptors do not distinguish between the body's own hormones and natural hormones. Therefore natural hormones do not compete with endogenous hormones for receptor sites; rather they supplement and balance the endogenous hormones. In contrast, the synthetic hormones used in conventional HRT are processed and synthesized from chemicals or animal products and are not chemically or biologically identical to human hormones. Synthetic hormones can compete with or replace the body's own hormones because some receptors mistake them for endogenous hormones.
Prescription-strength natural hormones usually are produced from stigmasterol extracted from soybeans. They are chemically altered so as to be bioidentical to human forms such as progesterone or the human estrogens. Progesterone and testosterone may be micronized for NHRT. Over-the-counter (OTC) natural progesterone creams usually are derived from diosgenin extracted from the giant Mexican yam. NHRT hormones are manufactured for pharmaceutical companies that make standard-dosage medications and for compounding or formulating pharmacies that make up individualized medications.
Testosterone is often supplied as DHEA. Pharmaceutical-grade DHEA is available without a prescription.
- oral capsules
- oral tablets
- gel caps
- lozenges, drops, or sprays that are absorbed through the mucous membranes under the tongue
- transdermal creams and gels applied to the skin
- injectable solutions
Estradiols are available as skin patches (Estraderm, Vivelle, Climera) that slowly and continuously release estrogen through the skin into the bloodstream, bypassing the liver. The patches are worn at all times and changed once or twice per week.
Oil-based micronized oral progesterone appears to be most-readily utilized by the body, since the oil protects the progesterone from stomach acids. Some research suggests that a natural vitamin-E base (tocopherol) is more effective and least toxic. Mineral-oilbased preparations may not be effectively absorbed and/or metabolized.
Testosterone as DHEA is available as:
- oral tablets
- transdermal or vaginal creams
NHRT creams and gels are absorbed rapidly through the skin in areas with high blood flow, such as the lower neck, upper chest, inner wrists, or hands. Lower dosages are used for NHRT creams and gels because they are absorbed into the bloodstream more efficiently than oral NHRT. Transdermal preparations bypass the gastrointestinal tract and the liver where side effects are more likely to occur. With creams and gels, individual dosages can be adjusted easily, according to symptom relief. Low-dosage natural progesterone creams are available without a prescription. However, absorption of transdermals is highly variable between patients. Those with dry skin, poor circulation, etc. absorb less transdermally. Studies also show that transdermal delivery of hormones may result if very high blood levels over time. More research is need in this area, but for this reason some physicians do not prefer transdermal delivery forms.
Some NHRTs mix highly concentrated estrogen, progesterone, and sometimes testosterone in a propylene glycol base for rapid absorption through the skin. Only one to four drops are required daily, costing as little as $70 per year.
Forms of NHRT
Typical NHRTs include:
- estradiol gel applied daily
- micronized ethinyl estradiol (Estrace) as 0.3–2.5-mg daily tablets
- estriol (80%) and estradiol (20%) as 1.25- or 2.3-mg twice-daily tablets (Biestrogen)
- estriol (80%), estradiol (10%), and estrone (10%), as a 2.5–5% gel applied daily (Triest), or as 1.25- or 2.5- mg, twice-daily tablets (Triestrogen)
- micronized progesterone as 50-, 100-, or 200-mg peanut-oil-based tablets or capsules (oral micronized progesterone, Prometrium)
- micronized progesterone as a 5% cream (percutaneous progesterone cream) or gel
- combined NHRT as 1.25-mg Triestrogen tablets and oral micronized progesterone (50–100 mg), twice daily
- oral micronized testosterone as 1.25–5-mg tablets
- micronized testosterone as a 1% cream or gel (Androgel), applied to the inner thigh or scrotum once or twice daily
Vaginal creams, tablets, and rings are not significantly absorbed into the bloodstream. However they can be useful for treating menopausal symptoms such as urinary problems, vaginal dryness, and thinning of the vaginal wall, which can cause painful intercourse. Vaginal NHRTs include:
- micronized estriol cream, 0.5 mg per g of base (Estriol)
- micronized estradiol cream, 1 mg per g of base (Estrace)
- estradiol as a silicone ring with a 2-mg reservoir, changed every 90 days (Estring)
- progesterone gel, 4 or 8% (Crinone)
Most effective NHRTs require a prescription and may be covered by insurance.
Women's symptoms & NHRT
The dosages and duration of NHRT vary according to response, as determined by symptom relief. Dosages in women may be cycled to correspond to the menstrual cycle.
Symptoms of hormone imbalance in teenagers and young women with normal menstrual cycles include:
A typical NHRT is micronized progesterone cream, 4–6 mg per kg (2.2 lb) body weight, rubbed daily on the neck, upper chest, and inner wrists, for the entire month or for two weeks prior to menstruation, depending on symptoms. It is not used on the face in the presence of acne.
Symptoms of hormone imbalances in women in their twenties and thirties with normal menstrual cycles, in addition to the above, may include:
- occasional or postpartum (after giving birth) depression
- bloating from salt and fluid retention
- migraine headaches
- breast tenderness
- decreased attention span
- weight gain
- food cravings
Typical NHRTs for three months to one year:
- micronized progesterone cream, 4-6 mg per kg (2.2 lb) body weight, daily
- estradiol, 6–8 MICROg per kg body weight.
In addition to the above symptoms, hormone imbalances in premenopausal women (aged 35 to over 40), with regular or irregular menstruation, may cause:
Typical NHRTs for three months to one year:
- Micronized progesterone, 4–6 mg per kg (2.2 lb) body weight, daily
- Estradiol, 7–9 micro;g per kg (2.2 lb) body weight, daily
NHRT may be particularly appropriate for perimenopausal symptoms in women aged 40–55. Their symptoms can be similar to those listed above, but may be more pronounced. Menstruation may have ceased or cycles may be irregular. Typical NHRTs:
- micronized progesterone cream, 5–7 mg per kg (2.2 lb) body weight
- estradiol, 6–9 MICROg. per kg (2.2 lb) body weight
- testosterone cream, 10 MICROg per kg (2.2 lb) body weight, applied to the labia and around the clitoris
Daily NHRT is continued for two to four months, followed by a five-day break.
Menopausal and postmenopausal women (usually aged 55 or older) may have, in addition to any of the above symptoms:
- micronized progesterone cream, 5–7 mg per kg (2.2 lb) body weight, daily
- estradiol, 6–9 MICROg per kg (2.2 lb) body weight, daily.
Men's symptoms and NHRT
Symptoms of low testosterone levels or hormone imbalances in andropausal men are very similar to those in women. Additional symptoms may include:
- nighttime urination
- impotence or decreased ability to maintain an erection
- decrease in muscle-building ability
- inability to lose weight
A natural androgen replacement protocol, lasting 3–14 months, might consist of:
- pine pollen, 0.5–5 gm, once or twice daily; a one-quarter-teaspoon tincture, three times daily; 5–10 gm daily in warm milk, in Chinese and Korean medicine
- David's lily flower, one-quarter-teaspoon tincture, twice daily
- Panax/tienchi ginseng tincture, one-third teaspoon daily
- nettle root (Urtica dioica), 300–1,200 mg daily
- tribulus (Tribulus terrestris), 250–500 mg standardized extract as pills or tablets, three times per day
- pregnenolone, a primary steroid hormone (prohormone) in men and women, 5–50 mg daily
- androstenedione (andro), 50–100 mg, one to three times per day, as a pill dissolved under the tongue
- androstenediol (andiol, 4-andiol, androdiol), 100 mg once or twice daily
- DHEA, 25–50 mg daily
- zinc, 20–40 mg daily
- celery juice, daily from three fresh stalks
- a diet high in oatmeal, corn, and pine nuts
Zinc is required for the transformation of androstenedione to testosterone. Zinc preparations usually include copper to prevent copper depletion.
Ginseng as an androgen replacement:
- Asian ginseng as 1–9 gm daily tablets
- Asian white (20–40 drops) and Kirin or dark red (5–20 drops) as a daily tincture
- Asian ginseng combined with tienchi (Panax pseudoginseng), one to one, one-third teaspoon daily in water
- Siberian ginseng
Foods & supplements
Most researchers believe that the human body cannot utilize the phytoestrogens in soy or the progesterone in yams; nor can the body transform these phytohormones into biologically available hormones. However some researchers believe that phytoestrogens called isoflavones (genistein and daidzein) found in soy can serve as short-term estrogen supplements. Soy protein in a low-fat diet reduces the risk of heart disease and isoflavones may help prevent bone loss. Isoflavones are found in tofu, tempeh, and soy drinks but not in soy oil.
Wild Mexican yam creams may contain phytoestrogens; however they are ineffective as progesterone supplements because they contain only a progesterone precursor which is inactive in the human body.
Phytoandrogens have been reported to increase androgen levels and the androgen-to-estrogen ratio in men. Foods containing high levels of phytoandrogens:
Foods that lower androgen levels and suppress androgenic activity in men include:
Blood hormone levels may be measured before and/or during NHRT:
- Follicle-stimulating hormone (FSH): high FSH levels indicate low sex hormone production and menopause.
- Estrogen blood tests measure how much of one type of estrogen is circulating in the blood and the total amount present in the bloodstream. However most estrogen in the body is bound to other molecules or cell receptors and cannot be measured.
Other tests include:
- Saliva hormone testing: inexpensive as performed by mail-order laboratories or with home test kits
- Urine testing reveals how much hormone is excreted through the kidneys over a 24-hour period. It is expensive and may be difficult to interpret.
- Yearly bone mineral density tests for those using NHRT to improve bone density
- Annual pelvic ultrasounds can be used to monitor the effectiveness of NHRT. These tests are inexpensive and enable the physician to view the thickness of the uterine lining and the shape of the ovaries, both of which are affected directly by estrogen and progesterone. Pelvic ultrasound also can detect and monitor ovarian cysts that may develop with hormone therapies.
Testosterone and/or DHEA levels in the blood or saliva are monitored regularly when DHEA is used in NHRT. However hormone levels are constantly changing and most tests reflect only the measurable hormone present at a single point in time.
Although they are approved by the U. S. Food and Drug Administration, natural hormones are not regulated as drugs. Most large manufacturers use standardized labeling and dosages of active ingredients. Nevertheless, the bioavailability—the amount of active ingredient that enters the bloodstream and can be utilized effectively—
NHRTs, especially androgen replacement, have not been well-studied. There have been no clinical safety trials. It is not known whether NHRT carries risks similar to some HRTs, including increased risk for breast cancer, coronary heart disease, stroke, and pulmonary embolism (a blood clot in an artery of the lung). Androgen replacement therapies should not be used by adolescent males.
Some synthetic hormone products may be labeled as "natural" because they are synthesized from naturally occurring substances. For example, synthetic estrogen is manufactured from the urine of pregnant horses. Some prescription hormones contain bioidentical estrogen but synthetic progesterone.
There have been very few reports of side effects from NHRT in women. Since the estrogens used in NHRT are bioidentical to human estrogens and tend to be weaker than the synthetic estrogens used in HRT, they are expected to have fewer side effects. Furthermore, NHRT can be halted and resumed at any time without side effects.
Natural androgen replacement therapy may cause irritability and other side effects in men, particularly in coffee-drinkers. Ginseng has many side effects and should be used with caution. Very high zinc intake also can have numerous side effects.
Research & general acceptance
The few research studies that have included NHRT have had positive results. NHRT practitioners claim that it is safer and more effective than HRT.
Training & certification
Most NHRTs are available only as prescriptions from a medical or naturopathic physician or nurse practitioner. Most doctors who use NHRT rely on personal research and the experiences of their patients.
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American Menopause Foundation. 350 Fifth Ave., Suite 2822, New York, NY 10118. (212) 714-2398. <http://www.americanmenopause.org>.
National Women's Health Information Center. 8550 Arlington Blvd., Suite 300, Fairfax, VA 22031. (800) 994-9662. <http://www.4woman.gov>.
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Margaret Alic, PhD